One of the areas in which technological advances have significantly enhanced surgery involves the use of synthetic materials for implantation in the body to assist in surgical reconstruction and repair. Biomaterials of synthetic polymeric origin are now widely accepted for tissue related applications, as tissue regeneration matrices, as tissue adhesives, as drug delivery matrices, in the prevention of surgical adhesions, for coating surfaces of synthetic implants and as tissue augmentation material. A lot of work has been done in the development of polymeric systems which can be applied as liquids which crosslink in situ to form biomaterials at the site of need on and/or in the body. Depending on the chemical structure of the precursor components and their stoichiometry, the biomaterials have varying physical and chemical properties.
Orthopedic Surgery
Orthopedic surgery has historically been the most significant application for biomaterials. It addresses medical concerns in the musculoskeletal system and the treatment of diseases and disturbances to its components, particularly bones, cartilage, ligaments, and tendons. The musculoskeletal system produces movement and responds to forces, therefore it is susceptible to injury and stress-related diseases, which can devastatingly affect the mobility. Any replacement and enforcement of these tissues has to perform in the same mechanical environment, and attainment of the relevant mechanical performance is not trivial. Further, as part of the aging process, tissue changes its shape and consistency. In particular, some tissues lose their form; thus augmentation or restoration is desirable. The loss of bone mass and stability, as occurs in osteoporosis, can be particularly devastating to an individual. A number of other diseases also disturbs the bone and joint function, leading to pain, loss of movement, or loss of vital function. One such prominent example is osteoarthritis, which is largely a mechanical disruption to the cartilage and underlying bone at the joints.
Hard Tissue Augmentation
Although a biomaterial used for augmenting hard tissue can be applied in different ways, a particular preferred way is through minimal invasive surgery. Compression fractures are particularly problematic in osteoporotic women. Minimally invasive surgery is the procedure of choice for treating vertebral compression fractures or osteoporotic vertebrae. This treatment is known as vertebroplasty. Before vertebroplasty was developed, surgeons did not treat compression fractures because intervention in these patient cases was risky and only inadequate tools were available. Vertebroplasty, a procedure in which the vertebral body is filled percutaneously with polymethylmethacrylate (PMMA) was developed to fulfill the treatment gap.
PMMA is mainly known as bone cement and is used off-label in this indication. PMMA is a hard, brittle polymer, tolerated by tissues and generally resistant to degradation. PMMA as used in vertebroplasty is a powder liquid system (PMMA co-polymer/monomeric methylmethacrylate) mixed in the operation room to a viscous paste and pulled up in to a syringe immediately prior to injection into the vertebra.
Vertebroplasty is a very effective treatment for compression fractures. It relieves pain in the majority of cases by preventing the micro-movement of the spongy tissue structure inside the vertebra and providing mechanical stabilization of existing microfractures (Mathis J. et al., Am. J. Neuroradiol. 22: 373-381 (2001)). The risk factors and problems in vertebroplasty are mainly associated with the toxicity of methylmethacrylate. The highly toxic methylmethacrylate may leach out into the blood stream before it is crosslinked sufficiently, causing blood pressure drop and migration of the bone cement into the veins with the possibility of ending up in the lungs or causing hypotension. Although this is a risk common to all uses of PMMA, it is increased in vertebroplasty due to the fact that PMMA is injected under pressure into a closed space inside fractured bone. This increases the risk for leakage. The exothermic polymerization process is a further deficiency of PMMA since it often leads to substantial damage of the surrounding tissue. Thus, PMMA is far from the ideal biomaterial for hard tissue augmentation, in general, and for application in vertebroplasty, in particular.
Handling is also an issue. The final preparation of the PMMA mixture has to be performed in the operation room. The individual components are measured, mixed to a homogenous mixture and the mixture is filled into the appropriate device for application, which is a syringe in the case of vertebroplasty. This procedure is time-consuming, susceptible to mistakes and bears health hazards for the person preparing the PMMA caused by inhalation of the powder during mixing and the volatile methylmethacrylate.
Even after successful injection and polymerization, PMMA can cause complications. PMMA is very hard and can cause stress-shelding and/or collapse of the vertebrae adjacent to the treated vertebra which then may fracture as well. (Ferguson S. et. al, Transactions of the 47th Annual Meeting of the ORS, 0280 (2001)).
Compositions which have to form biomaterials at the site of injection in the human or animal body and which have to augment osteoporotic vertebrae have to comply with various needs. First, the treatment should reduce or completely remove the pain associated with fractured vertebrae so that the patient can leave the bed. Second, the mechanical properties of the osteoporotic vertebra must be improved. This is evident when comparing compressive strength and Young's modulus E of a young healthy vertebra (vertebra in its ideal state) to an osteoporotic vertebra. The compressive strength of the spongy inner part of an ideal vertebra can be up to eightfold greater than that of an osteoporotic vertebra. Similarly, the Young's modulus E of the spongy part of an ideal vertebra can be up to a hundredfold greater than the Young's modulus E of an osteoporotic one. It is accepted that the mechanical properties of an ideal vertebra can hardly be re-established but people suffering from osteoporosis are mainly at an advanced age and do not seek to undertake great physical efforts which require the presence of ideal vertebrae. Thus as long as the patient is free of pain and has regained mobility to a substantial part of his vertebrae, the treatment is successful.
Biomaterials which are made from polymeric hydrophilic systems, such as PEG derivatives, have been described in the prior art, such as in U.S. Pat. Nos. 5,626,863; 6,166,130; 6,051,648; 5,874,500; 6,258,351 and in WO 00/44808. These biomaterials are not suitable for use in hard tissue augmentation due to their lack of mechanical performance, such as strength and stiffness and due to extensive swelling. Uncontrollable swelling makes biomaterials unacceptable for application in limited spaces as in vertebrae. The material expands and can press against nerves, such as the spinal cord, or protrudes uncontrollable from the place of injection.
Therefore, there exists a need for new biomaterials which can be used for hard tissue augmentation. In particular due to the growth in the elderly population, there is a need for a replacement of PMMA in vertebroplasty.
It is therefore an object of the present invention to provide a biomaterial for tissue augmentation.
It is a further object of the present invention to provide a biomaterial for hard tissue augmentation, preferably as a replacement for PMMA.
It is a further object to provide an augmentation material for use in vertebroplasty which does not have the disadvantages and risks associated with the use of PMMA.